The structural nature of the onco-fetal forms of cytosolic NAD-linked glycerol-3-phosphate dehydrogenase that we have observed in neoplastic tissues in rabbits and mice will be determined by isolation from P388 murine leukemia cells, and structural comparison with the multiple forms we have characterized from normal tissues in both species. Whether the onco-fetal forms are characteristic only of cancerous and fetal tissues or rather function in dividing normal cells will be determined by examination of enzyme forms in intestinal mucosa cells, mitogen stimulated lymphocytes, and antigen-activated mouse spleen cells. The metabolic function of the onco-fetal forms will be examined by determination of kinetic parameters, and examination of potential inhibitors and regulators. Potential exploitation of onco-fetal forms of enzymes in general in neoplasia and of onco-fetal glycerol-3-dehydrogenase in particular will be tested by use of antibodies to the murine leukemia enzyme enclosed in liposomes and applied in cell culture against P388 leukemia cells. Potential in vivo utility of liposome enclosed antibodies will also be examined. Differential inhibitors and regulators of the oncofetal enzymes will be examined for chemotherapeutic effect in culture and in vivo. Antibodies will be prepared to the flavin-linked mitochondrial glycerol-3-P dehydrogenase that we have isolated in homogenous form from rabbit muscle and brain mitochondria. The antibodies will be employed to isolate and characterize the flavin-linked enzyme from rabbit Brown-Pearce carcinoma mitochondria in order to determine whether tumor mitochondria express protein structures in this case distinct from those in normal tissue mitochondria. Potential development of mitochondrially based chemotherapy by exploitation of biochemical differences between normal and neoplastic cell mitochondria depends on the discovery of such differences if they exist. In addition to contributing to potential cytoplasmic and mitochondrial isoenzyme directed therapy, these studies may permit the application of oncofetal forms in conjunction with hemoglobin synthesis in the Friend erythroleukemia system as markers of normal and neoplastic differentiation in the search for agents promoting non-malignant differentiation of malignant cells.